Method and Composition for In Situ Formation and/or Expansion of a Polymer-Based Hemostatic Agent to Control Bleeding

ABSTRACT

A composition for in situ formation and/or expansion of a polymer-based hemostatic agent to control bleeding includes a suitable amount of a polymer or polymer-forming component, hydrogen peroxide or chemical(s) capable of forming hydrogen peroxide, or a combination of both, and a decomposing agent for hydrogen peroxide. The decomposing agent includes an endogenously or exogenously supplied catalyst (other than catalase), or both, and/or the polymer or polymer-forming component.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation application of U.S. application Ser. No.12/314,718, filed Dec. 16, 2008, which is a continuation-in-part (CIP)of application Ser. No. 12/073,822, filed Mar. 11, 2008, both of whichare hereby incorporated herein in their entirety by reference.

FIELD AND BACKGROUND OF THE INVENTION

The present invention is generally directed to hemostatic compositionsand methods employing the same, the delivery of agents into or untowounds and/or body cavities, and more particularly to a composition andmethod for controlling bleeding at wound sites through in situ formationand expansion of a polymer-based hemostatic agent.

One of the major causes of death is uncontrolled or inadequatelycontrolled loss of blood due to traumatic injury, accidental orotherwise. The blood loss may be internal or external and, when notrestricted or controlled quickly, can be fatal. It is, therefore,critical to restrict, arrest, or control blood loss by managing a woundby, for example, creating a physical obstruction or improving thedelivery of a hemostatic agent to the bleeding vessel(s). Various priorart methods and compositions disclose the medical use of hydrogenperoxide as an antiseptic for wounds or as a hemostasis-promoting agent,or as a both, e.g., U.S. Pat. No. 5,846,567, as a vapor for thedispersal or creation of a gel, and U.S. Pat. No. 5,667,501, forstimulating action of hydrogen peroxide in fibroblast proliferation andits application in wound dressing.

OBJECTS AND SUMMARY OF THE INVENTION

The principal object of the present invention is to provide acomposition and method for reducing, restricting, and/or arresting,(collectively “controlling”) hemorrhage from wounds, internal orexternal, in humans and other animals.

Another object of the present invention is to provide a composition andmethod for in situ formation of an artificial blockage to controlbleeding.

Another object of the present invention is to provide a composition andmethod for a more efficient delivery of chemical and/or biologicalhemostatic agents to wound surfaces and other surfaces capable ofabsorbing the hemostatic agents.

Another object of the present invention is to provide a composition andmethod for controlling bleeding due to any traumatic injury, deliberate,as in a medical procedure, or accidental. The invention works by, one ormore of 1) increasing the efficiency of delivery or dispersal ofhemostatic and/or other wound-treatment agent(s), and/or any otherclinically or medically relevant agent via the selective ornon-selective expansion of substance(s) containing the agent(s); 2)providing a pressurized wound or other compartment with material thatwill restrict blood flow and loss within and from the compartment; 3)providing antiseptic in the form of unreacted hydrogen peroxide to thesurface(s) and space(s) of a wound or other body space; 4) providingmeans for the creation of an artificial clot, tamponade, or obstructionthat can fill the wound space or other body space efficiently; 5)providing an agent, such as hydrogen peroxide that causes or accelerateshemostasis; 6) providing excess oxygen where it may aid in initialhealing; 7) in certain cases, providing the chemical basis foraccelerating or making possible other chemical reactions, produced fromextraneously applied chemicals or from endogenous (originating from thebody itself) chemicals, leading to formation of an expanding substance,foam, or obstruction to bleeding, or any combination of two or more ofthe three, and 8) in the case of treatment of wounds, stemming ofbleeding by expanding the hemostatic material when it surrounds orencloses one or more blood vessels, including arteries and veins,thereby pinching or clamping them partially or completely.

Another object of the present invention is to provide a composition andmethod for controlling bleeding, which relies, in part, on aninteraction between hydrogen peroxide and one or more chemical agent(s)including, but not limited to, a catalyst, or a polymer orpolymer-forming agent, that is delivered to a wound or body cavity,preferably substantially simultaneously or in sequence, to produceoxygen or other gas, which serves as a blowing agent for the expansionof a polymer-based material, that in turn actively fills a wound spaceor other body cavity to produce a hemostatic effect or effects, or toproduce other effect(s) of medical, surgical, or clinical significance.Alternatively, some, most, or all of the hydrogen peroxide may interact,instead of or in addition to, with endogenously produced catalase, thelatter enzyme being released inside or upon the wound because ofdistribution of the leaked blood and other body fluids, so thatexpansion of the substance or agent applied to the wound or other bodyspace or area will result in a fully or partially self-regulatingprocess, whereupon the oxygen-releasing reaction(s) preferentially willoccur in those locations where it is needed the most.

Another object of the present invention is to provide a composition andmethod for controlling bleeding, wherein one or more agents, includinghydrogen peroxide, are administered to a wound or other body space orsurface, causing expansion or foaming of an administered substancethereupon, due to oxygen release caused by the reaction of hydrogenperoxide with one or more catalysts, or the reaction of hydrogenperoxide with one or more polymers or polymer-forming agents. Theresulting expanded substance produced by any of the aforementioned meansmay be a viscous liquid, semi-solid, or solid substance that acts as anartificial blood clot or clog under pressure, stemming the flow of bloodfrom the wound, as in the case of viscous drag. Examples of suchexpanded substances include: polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, polyethylene amine, polyacrylamide,polysiloxanes, polyvinylsiloxane, vinyl polysiloxane, resins,polylysine, chitosan, polysaccharide, whey protein, casein, albumin,collagen, gelatin, a polypeptide or protein possessing reactive groupscapable of cross-linking to isocyanates, diisocyanates, or othermolecules, starch, cellulose, polylactic acid, polyols, an inorganicpolymer, and a combination thereof. The foaming action produced by theoxygen released by the interaction between hydrogen peroxide and otherchemicals may also be supplemented by the generation of another gas orother gases, or by oxygen released by another mechanism or from asubstance other than hydrogen peroxide. The gas(es) generated maycomprise oxygen, carbon dioxide, a nitrogen oxide, methane, ethane,ethylene, propane, or a combination thereof.

Another object of the present invention is to provide a method forincreasing the temperature of the wound surface and of the associatedblood for thermally accelerating the natural clotting of blood. Theincrease in temperature results from the exothermic chemical reactionsoccurring from the interaction of chemical agents present in thehemostatic composition.

Another object of the present invention is to provide a method forchemical stimulation of hemostasis by agents, including, but not limitedto, hydrogen peroxide, present in a component of the invention.

Another object of the present invention is to provide a method forthermally inducing heat-shock in proteins or other indigenous biologicalfactors, thereby improving healing of the wound subsequent toapplication of the invention. The increase in temperature results fromthe exothermic chemical reactions occurring from the interaction ofchemical agents present in the hemostatic composition.

Another object of the present invention is to provide a kit for in situformation of an artificial blockage to control bleeding in a wound orbody cavity.

In summary, the present invention provides a method and composition forcontrolling bleeding, internal or external, by in situ formation of ablockage, and for delivering agents that are chemically and thermallyhemostatic. The method may be applied consecutively more than once tothe wound or body cavity, within a space of time varying between 0.1second and one year.

One of the above objects is met, in part, by the present invention,which in one aspect includes a composition for in situ formation andexpansion of a polymer-based hemostatic agent to control bleeding. Thecomposition includes a suitable amount of a polymer or polymer-formingcomponent, hydrogen peroxide or chemical(s) capable of forming hydrogenperoxide, or a combination of both, and a decomposing agent for hydrogenperoxide. The decomposing agent includes exogenous or endogenouscatalyst other than catalase, or both. The composition may also includeone or more anesthetics, one or more procoagulant(s) or coagulants, oneor more vasoconstrictors, and one or more clotting agents of inorganicorigin. Anesthetics may be at least one member taken from the group oftetracaine, lidocaine, benzocaine, and procaine. Procoagulants orcoagulants may be at least one member from the group consisting oftissue factor, Factor VII, Factor VIIa, prothrombin, thrombin, FactorXII, Factor XIII, Factor XIIIa, fibrinogen, fibrin monomer, fibrinmultimer, crosslinked fibrin, and exothermically produced heat.Vasoconstrictors may be at least one member from the group consisting ofoxymetazoline, an oxymetazoline derivative, phenylephrine,phenylpropanolamine, nicotine, pseudoephedrine, ephedrine, an ephedrinederivative, and a combination thereof. Clotting agents of inorganicorigin may be at least one or more agents taken from the group ofsilicates, peroxides, cations, anions, and inorganic polymers.

Another aspect of the present invention includes a composition for insitu formation and expansion of a polymer-based hemostatic agent tocontrol bleeding. The composition includes a suitable amount of apolymer or polymer-forming component, hydrogen peroxide or chemical(s)capable of forming hydrogen peroxide, or a combination of both, and adecomposing agent for hydrogen peroxide. The polymer or polymer-formingagent comprises and/or also functions as the decomposing agent.

Another aspect of the present invention includes a composition for insitu formation of an artificial blockage to control bleeding, whichincludes an expandable component, a gas-generating agent, and anendogenous or exogenous catalyst other than catalase, or both.

Another aspect of the present invention includes a composition for insitu formation of an artificial blockage to control bleeding, whichincludes a polymer or polymer-forming component, a gas-generating agent,and a decomposing agent for the gas-generating agent.

Another aspect of the present invention includes a method for in situformation of an artificial blockage in a wound or body cavity, whichincludes providing a suitable amount of a polymer or polymer-formingcomponent, providing hydrogen peroxide, delivering the polymer orpolymer-forming component and hydrogen peroxide in a wound or bodycavity, and allowing the hydrogen peroxide to come in contact with anendogenous or exogenous catalyst other than catalase to produce anexpanded mass. The polymer or polymer-forming component may be at leastone member selected from the group consisting of polyacrylate, polyvinylalcohol, polyvinyl pyrrolidone, polyethylene glycol, polyethylene amine,polyacrylamide, polysiloxanes, polyvinylsiloxane, vinyl polysiloxane,resins, polylysine, chitosan, polysaccharide, whey protein, casein,albumin, collagen, gelatin, a polypeptide or protein possessing reactivegroups capable of cross-linking to isocyanates, diisocyanates, or othermolecules, starch, cellulose, polylactic acid, polyols, an inorganicpolymer, and a combination thereof. An optional crosslinking agent maybe at least one member selected from the group consisting of phosphoricacid, boric acid, glutaraldehyde, acetaldehyde, a diisocyanate, acarbodiimide, a resin, a polymer, calcium ion, Genipin, and acombination thereof. The polymer formed comprises at least one memberselected from the group consisting of polyacrylate, polyvinyl alcohol,polyvinyl pyrrolidone, polyethylene glycol, polyethylene amine,polyacrylamide, polysiloxanes, polyvinylsiloxane, vinyl polysiloxane,resins, polylysine, chitosan, polysaccharide, whey protein, casein,albumin, collagen, gelatin, a polypeptide or protein possessing reactivegroups capable of cross-linking to isocyanates, diisocyanates, or othermolecules, starch, cellulose, polylactic acid, polyols, an inorganicpolymer, and a combination thereof.

Another aspect of the present invention includes a method for in situformation of an artificial blockage in a wound or body cavity, whichincludes providing a suitable amount of a polymer or polymer-formingcomponent, providing hydrogen peroxide, and delivering the polymer orpolymer-forming component and hydrogen peroxide in a wound or bodycavity and allowing a reaction therebetween to produce an expanded mass.

Another aspect of the present invention includes a method for in situformation of an artificial blockage in a wound or body cavity, whichincludes providing a first component comprising a gas-generating agent,providing a second component comprising an expandable component,delivering the first and second components into a wound or body cavity,allowing the gas-generating agent to produce a gas, and allowing the gasto come in contact with the expandable component thereby producing anexpanded mass.

Another aspect of the present invention includes a method for in situformation of an artificial blockage in a wound or body cavity, whichincludes providing a first component comprising a gas-generating agent,providing a second component comprising an expandable component,providing a third component comprising a catalyst other than catalase,delivering the first, second and third components into a wound or bodycavity, allowing the catalyst to come in contact with the gas-generatingagent thereby producing a gas, and allowing the gas to come in contactwith the expandable component thereby producing an expanded mass.

Another aspect of the present invention includes a kit for in situformation of an artificial blockage in a wound or body cavity, whichincludes a first component including hydrogen peroxide, a secondcomponent including an expandable polymeric component, and instructionsfor using the components.

Another aspect of the present invention includes a kit for in situformation of an artificial blockage in a wound or body cavity, whichincludes a first component including hydrogen peroxide, a secondcomponent including an expandable polymeric component, a third componentincluding a catalyst other than catalase, and instructions for using thecomponents.

BRIEF DESCRIPTION OF THE DRAWINGS

One of the above and other objects, aspects, novel features andadvantages of the present invention will become apparent from thefollowing detailed description of the preferred embodiment(s) ofinvention, illustrated in the accompanying drawings, wherein:

FIG. 1 is a schematic illustration of an exemplary reaction inaccordance with an embodiment of the present invention;

FIG. 2 is a schematic illustration of another exemplary reaction betweenvarious components in accordance with another embodiment of the presentinvention; and

FIG. 3 is an illustration of a formative action of the composition inaccordance with an embodiment of the invention, showing expansion due tothe interaction between hydrogen peroxide and a polymer and/or catalyst,such as platinum.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT(S) OF THE INVENTION

A preferred embodiment of the present invention is based, in part, on aninteraction between hydrogen peroxide and a catalyst (other thancatalase) or between hydrogen peroxide and a reactant, such as a polymeror polymer-forming agent, to generate or drive a foam, an expandablematerial, or other substance into a wound space or other body cavity.

One embodiment of the method described herein is conveniently referredto as hydrogen peroxide reaction-driven expansion, dispersal, andspatial configuring of wound with hemostatic and/or other woundtreatment agent(s) that can be delivered into any body cavity or space,including wounds. The method can be applied to both humans and animals.

The method allows filling of wound or other space, including a bodyspace or cavity, open to the air or otherwise, to allow coating of abody surface with a substance in the form of foam, sponge, or othermaterial by pressure produced through the release of oxygen or other gasconsequent to the reaction of a chemical component delivered at the sameor about the same time as hydrogen peroxide. With this method, an agentor substance, containing hydrogen peroxide, when injected through theopening of a wound or other space or cavity in the body, will expand,disperse, or configure (collectively “expand”) to fill the wound orother space, when the agent encounters one or more of the following:another substantially simultaneously delivered agent, such as a polymeror polymer-forming agent, or a catalyst, for polymer formation and/orthe breakdown of hydrogen peroxide, and a wound surface or space, blood,or another body fluid, thus assisting hemostasis by effecting animproved delivery of a hemostatic agent, while at the same time causinga pressurized obstruction to bleeding or other physiological flow.

Alternatively, a binary or ternary system of two or three components,respectively, preferably one containing a catalyst (other than catalase)and/or other chemical capable of reacting catalytically or otherwisewith hydrogen peroxide, when injected or forced into a wound space orother body cavity substantially simultaneously, will react to drive,separately or together, the two or three components of the system, ortheir reaction products, into or unto the wound or other body space,distributing the agents to where most needed, while at the same timecreating a physical obstruction that restricts blood loss. Specifically,a two-component system will preferably include hydrogen peroxide and apolymer or polymer-forming agent, while a three-component system willadd a catalyst (other than catalase) as the third component.

One embodiment of a method for delivery of the hydrogen peroxide andother substances into the wound or other body space will preferably beeffected through compression of a pliable tube or piston-dependentdelivery system containing the deliverable agents, so that hydrogenperoxide and other agents will pass into the wound space or other bodyspace, although other suitable means may also be employed. Typically,one or more small tubing extension(s) or mixer(s) from the deliverydevice will be fed into the wound or other body area or space toaccomplish the method. Once the agent, containing the hydrogen peroxide,makes contact with an agent capable of reacting with hydrogen peroxideto release oxygen or other gas, foaming or expansion of the appliedagent will result, filling the space in the wound or other body space.The foam may, over time, harden or become more viscous, includingtransforming from one phase to another, such as from liquid tosemi-solid or solid, and may include polymer(s) or polymer-formingingredient(s), creating an artificial clot or clog, driven into placeand shaped by the release of oxygen and/or other gas resulting from theinteraction between hydrogen peroxide and a catalyst other thancatalase, and/or partially or completely from the interaction betweenhydrogen peroxide and other agent(s) comprising the hemostatic product.The method may be applied consecutively more than once to the wound orbody cavity, within a space of time varying between 0.1 second and oneyear.

Preferably, two or three components will be mixed just prior to or afterinjection, insertion, or any other kind of application to a wound space.At least one of these binary or ternary components will contain hydrogenperoxide at a concentration of about 0.000001% to about 100% by volumeor weight, with a preferred range of about 1% to about 20%, and a morepreferred concentration being about 2%.

One embodiment of the composition of the present invention preferablyincludes at least one expandable component, such as a polymer, polymerprecursor or polymer-forming agent taken from the group consisting of;polyacrylate, polyvinyl alcohol, polyvinyl pyrrolidone, polyethyleneglycol, polyethylene amine, polyacrylamide, polysiloxanes,polyvinylsiloxane, vinyl polysiloxane, resins, polylysine, chitosan,polysaccharide, whey protein, casein, albumin, collagen, gelatin, apolypeptide or protein possessing reactive groups capable ofcross-linking to isocyanates, diisocyanates, or other molecules, starch,cellulose, polylactic acid, polyols, an inorganic polymer, and acombination thereof; a gas-generating component, such as hydrogenperoxide; and a decomposing agent for the gas-generating agent. Thedecomposing agent includes an endogenous or exogenous catalyst, or both,and/or at least one polymer or polymer-forming agent, as noted before.Thus, the polymer or polymer-forming agent also functions as adecomposing agent.

The catalyst(s) used in an embodiment of the composition of the presentinvention, includes a metal ion, platinum, triethylenediamine (TEDA,also known as 1,4-diazabicyclo[2.2.2]octane or DABCO),dimethylcyclohexylamine (DMCHA), dimethylethanolamine (DMEA),tetramethylbutanediamine (TMBDA), pentamethyldipropylenetriamine,N-(3-dimethylaminopropyl)-N,N-diisopropanolamine, 1,3,5-(tris(3-dimethylamino)propyl)-hexahydro-s-triazine, bis-(2-dimethylaminoethyl)ether, N-ethylmorpholine, triethylamine (TEA),1,8-diazabicyclo[5.4.0]undecene-7 (DBU), pentamethyldiethylenetriamine(PMDETA), benzyldimethylamine (BDMA), tetracaine, and a combinationthereof. The catalyst concentration can range from 0 to about 5,000milligrams/mL, with a preferred range of about 50 milligrams/mL to about350 milligrams/mL and a more preferred concentration of about 150milligrams/mL.

The medium bearing the components delivered by an embodiment of themethod of the invention can be of any state of matter, including liquid,gas, or solid, or any combination thereof.

Other agents in the composition may include polymers, organic orinorganic, polymer-forming ingredients, pre-polymers, linking agents,gas-generating agents other than hydrogen peroxide or catalase,procoagulants, coagulants, anesthetics, vasoconstrictors, catalystsother than catalase, enzymes other than catalase, pastes, liquids,organic or inorganic.

Examples of hydrogen peroxide decomposing in the presence of a catalyst,and a chemical reaction between hydrogen peroxide and a matrix componentof an embodiment of the composition used in the preferred method, areshown in FIGS. 1 and 2, respectively.

Non-limiting examples of polymer-forming polymers, include:polyacrylate, polyvinyl alcohol, polyvinyl pyrrolidone, polyethyleneglycol, polyethylene amine, polyacrylamide, polysiloxanes,polyvinylsiloxane, vinyl polysiloxane, resins, polylysine, chitosan,polysaccharide, whey protein, casein, albumin, collagen, gelatin, apolypeptide or protein possessing reactive groups capable ofcross-linking to isocyanates, diisocyanates, or other molecules, starch,cellulose, polylactic acid, polyols, an inorganic polymer, and acombination thereof.

Non-limiting examples of optional crosslinking agents, include:phosphoric acid, boric acid, glutaraldehyde, acetaldehyde, adiisocyanate, a carbodiimide, a resin, a polymer, calcium ion, Genipin,and a combination thereof.

Non-limiting examples of coagulants and procoagulants, include: tissuefactor, Factor VII, Factor VIIa, hydrogen peroxide, prothrombin,thrombin, Factor XII, Factor XIII, Factor XIIIa, fibrinogen, fibrinmonomer, fibrin multimer, crosslinked fibrin, and exothermicallyproduced heat.

Non-limiting examples of vasoconstrictors, include: oxymetazoline,oxymetazoline derivatives, phenylephrine, phenylpropanolamine, nicotine,pseudoephedrine, ephedrine, and ephedrine derivatives.

The system used to deliver any of the above-mentioned agents, includingthe agent hydrogen peroxide, to a wound or body cavity can be of anykind or property. The volume of the component(s) to be delivered, or thetotal volume of component(s) actually delivered, can range from about0.0000001 to about 10,000,000 milliliters (mL), with a preferred rangeof about 5 mL to about 60 mL, and a more preferred volume of about 30mL.

After allowing some time, preferably about 5 seconds to three minutes,or more preferably about 45 seconds, for expansion or pressurization ofthe component(s) or resulting component(s) in the wound space or bodycavity, the wound will be sealed with a suitable bandage. The amount oftime before application of the bandage can be from 0 to about 1,000,000seconds (sec) after delivery of the component(s), with a preferred rangeof about 1 sec to about 15 minutes (min), and a more preferred intervalof about 5 min.

An example of the mechanism of formation of the clotting material thatfills the wound and enhances delivery of matrix components, isillustrated in FIG. 3.

The composition of the present invention can be of any chemical orphysical nature or properties, and may include any organic or inorganicsubstance or combination of substances.

While this invention has been described as having preferred sequences,ranges, steps, materials, structures, components, features, and/ordesigns, it is understood that it is capable of further modifications,uses, and/or adaptations of the invention following in general theprinciple of the invention, and including such departures from thepresent disclosure as those come within the known or customary practicein the art to which the invention pertains, and as may be applied to thecentral features hereinbeforesetforth, and fall within the scope of theinvention and of the limits of the appended claims.

REFERENCES

The following references, and any cited in the disclosure herein, arehereby incorporated herein in their entirety by reference.

-   1. A. Brandt, C. M. Leir, D. J. Wirtanen, Spray Bandage and Drug    Delivery System, U.S. Pat. No. 6,958,154 (2005).-   2. M. J. MacPhee, W. N. Drohan, C. J. Woolverton, Supplemented and    Unsupplemented Tissue Sealants, Methods of their Production and Use,    U.S. Pat. No. 6,054,122 (2000).-   3. W. N. Drohan, M. J. MacPhee, H. Nunez, G. Liau, T. Maciag, W. H.    Burgess, Methods for Treating Wound Tissue and Forming a    Supplemented Fibrin Matrix U.S. Pat. No. 7,196,054 (2007).-   4. S. I. Miekka, W. N. Drohan, T. R. Jameson, J. R. Taylor,    Jr., M. P. Singh, M. J. MacPhee, Methods of Production and use of    Liquid Formulations of Plasma Proteins U.S. Pat. RE38431 (2004).-   5. K. C. Cochrum, S. Jemtrud, Hemostatic Compositions and Methods    for Controlling Bleeding U.S. Pat. No. 7,101,862 (2006).-   6. A. N. Kalloo, P. J. Paricha, Clot Dissolving Method, U.S. Pat.    No. 5,846,567 (1998).-   7. M. Fowler, T. R. Burrow, T. D. Turner, R. J. Schmidt, L. Y.    Chung, Wound Dressings, U.S. Pat. No. 5,667,501 (1997).-   8. B. S. Kheirabadi, D. Tuthill, R. Pearson, V. Bayer, D. Beall, W.    Drohan, M. J. MacPhee, J. B. Holcomb, Metabolic and Hemodynamic    Effects of CO₂ Pneumoperitoneum in a Controlled Environment, Journal    of Trauma Injury, Infection and Critical Care, 50, 1031-1043 (2001).-   9. J. B. Holcomb, J. M. McClain, A. E. Pusateri, D. Beall, J. M.    Macaitis, R. A. Harris, M. J. MacPhee, J. R. Hess, Fibrin Sealant    Foam Sprayed Directly on Liver Injuries Decreases Blood Loss in    Resuscitated Rats Journal of Trauma Injury, Infection and Critical    Care, 49, 246-250, (2000).-   10. D. D. Tuthill, V. Bayer, A. M. Gallagher, W. N. Drohan, M. J.    MacPhee, Assessment of Topical Hemostats in a Renal Hemorrhage Model    in Heparinized Rats, Journal of Surgical Research, 95, 126-132    (2001).-   11. Holcomb et al. Implications of a New Dry Fibrin Sealant    Technology for Trauma Surgery, Surgical Clinics of North America,    77, 944-952 (1997).-   12. H. B. Alam, G. B. Uy, D. Miller, E. Koustova, T. Hancock, R.    Inocencio, D. Anderson, O. Llorente, P. Rhee, Comparative Analysis    of Hemostatic Agents in a Swine Model of Lethal Groin Injury, The    Journal of TRAUMA, Injury, Infection, and Critical Care, 54,    1077-1082 (2003).-   13. R. G. Ellis-Behnke, Y-X. Liang, D. K. C. Tay, P. W. F.    Kau, G. E. Schneider, S. Zhang, W. Wu, K-F. So, Nano Hemostat    Solution: Immediate Hemostasis at the Nanoscale, Nanomedicine:    Nanotechnology, Biology, and Medicine; 2, 207-215 (2006).-   14. M. W. Chan, S. D. Schwaitzberg, M. Demcheva, J. Vournakis, S.    Finkielsztein, R. J. Connolly, Comparison of Poly-N-acetyl    Glucosamine with Absorbable Collagen, and Fibrin Sealant for    Achieving Hemostasis in a Swine Model of Splenic Hemorrhage, Journal    of Trauma Injury, Infection and Critical Care, 48, 454-7 (2000).-   15.1. Wedmore, J. G. McManus, A. E. Pusateri, J. B. Holcomb, Special    Report on the Chitosan-based Hemostatic Dressing: Experience in    Current Combat Operations, The Journal of Trauma Injury, Infection    and Critical Care, 60, 655-658 (2006).-   16. A. M. Pope, Editor, Fluid Resuscitation: State of the Science    for Treating Combat Casualties and Civilian Injuries, The National    Academy Press, (2000).-   17. A. E. Pusateri, J. B. Holcomb, B. S. Kheirabadi, H. B.    Alam, C. E. Wade, K. L. Ryan, Making Sense of the Preclinical    Literature on Advanced Hemostatic Products, The Journal of Trauma    Injury, Infection and Critical Care, 60, 674-682, (2006).-   18. H. B. Alam, Z. Chen, A. Jaskille, R. I. L. C. Querol, E.    Koustova, R. Inocencio, R. Conran, A. Seufert, N. Ariaban, K.    Toruno, P. Rhee, Application of a Zeolite Hemostatic Agent Achieves    100% Survival in a Lethal Model of Complex Groin Injury in Swine,    The Journal of Trauma Injury, Infection and Critical Care, 56,    974-983, (2004).-   19. B. S. Kheirabadi, E. M. Acheson, R. Deguzman, J. L.    Sondeen, K. L. Ryan, A. Delgado, E. J. Dick Jr., J. B. Holcomb,    Hemostatic Efficacy of Two Advanced Dressings in an Aortic    Hemorrhage Model in Swine, The Journal of Trauma Injury, Infection    and Critical Care, 59, 25-34 (2005).-   20. J. G. McManus, I. Wedmore, Modern Hemostatic Agents for    Hemorrhage Control—A Review and Discussion of Use in Current Combat    Operations, Business Briefing: Emergency Medicine Review, 76-79    (2005).

21. J. G. Montes, K. K. Rangan, R. Radhakrishnan, T. S. Sudarshan,Method and Composition for In Situ Formation of an Artificial Blockageto Control Bleeding, U.S. patent application Ser. No. 12/073,822 (2008).

What is claimed is:
 1. An injection method for in situ formation of apressurized obstruction in a wound or bleeding body cavity to controlbleeding, comprising the steps of: a) providing a polymer-formingcomponent comprising polyvinylsiloxane; b) providing hydrogen peroxidehaving a concentration of about 10% to 20% by volume or weight; c)delivering the polymer-forming component and hydrogen peroxide byinjection into the wound or body cavity; and d) allowing the hydrogenperoxide to come in contact an endogenous or exogenous catalystcomprising platinum, thereby producing an expanded mass within 5 secondsto 45 seconds forming a pressurized obstruction to control bleeding inthe wound or body cavity.
 2. The method of claim 1, wherein: thepolymer-forming component and hydrogen peroxide are provided in a volumeof about 0.1 mL to about 1000 mL.
 3. The method of claim 1, wherein: themethod may be applied consecutively more than once to the wound or bodycavity, within a space of time varying between 0.1 second and one year.4. The method of claim 1, wherein: the polymer-forming componentadditionally comprises at least one member selected from the groupconsisting of polyurethane, polysiloxane, polyacrylate, siloxane, vinylpolysiloxane, resin, an inorganic polymer, and a combination thereof. 5.The method of claim 1, wherein: the catalyst additionally comprises atleast one member selected from the group consisting of a metal ion,triethylenediamine (TEDA, also known as 1,4-diazabicyclo[2.2.2]octane orDABCO), dimethylcyclohexylamine (DMCHA), dimethylethanolamine (DMEA),tetramethylbutanediamine (TMBDA), pentamethyldipropylenetriamine,N-(3-dimethylaminopropyl)-N,N-diisopropanolamine, 1,3,5-(tris(3-dimethylamino)propyl)-hexahydro-s-triazine,bis-(2-dimethylaminoethyl)ether, N-ethylmorpholine, triethylamine (TEA),1,8-diazabicyclo[5.4.0]undecene-7 (DBU), pentamethyldiethylenetriamine(PMDETA), benzyldimethylamine (BDMA), tetracaine, and a combinationthereof.
 6. The method of claim 1, wherein: the expanded masssubstantially entirely fills up the wound or body cavity.
 7. The methodof claim 1, wherein: the expanded mass configures to assume the shape ofthe wound or body cavity.
 8. An injection method for in situ formationof a pressurized obstruction in a wound or bleeding body cavity tocontrol bleeding, comprising the steps of: a) providing a firstcomponent comprising hydrogen peroxide having a concentration of about10% to 20% by volume or weight; b) providing a second componentcomprising an expandable component comprising polyvinylsiloxane; c)providing a third component comprising a catalyst comprising platinum;d) delivering the first, second and third components by injection intothe wound or body cavity; e) allowing the catalyst comprising platinumto come in contact with the hydrogen peroxide thereby producing a gas;and f) allowing the gas to come in contact with the polyvinylsiloxanethereby producing an expanded mass within 5 seconds to 45 secondsforming a pressurized obstruction to control bleeding in the wound orbody cavity.
 9. The method of claim 8, wherein: the first, second andthird components are provided in a volume of about 0.1 mL to about 1000mL.
 10. The method of claim 8, wherein: the method may be appliedconsecutively more than once to the wound or body cavity, within a spaceof time varying between 0.1 second and one year.
 11. An injection methodfor in situ formation of a pressurized obstruction in a wound orbleeding body cavity to control bleeding, comprising the steps of: a)providing a polymer-forming component comprising polyvinylsiloxane; b)providing hydrogen peroxide having a concentration from 16% to 20% byvolume or weight; c) delivering the polymer-forming component andhydrogen peroxide by injection into the wound or body cavity; and d)allowing the hydrogen peroxide to come in contact an endogenous orexogenous catalyst comprising platinum, thereby producing an expandedmass within 5 seconds to 45 seconds forming a pressurized obstruction tocontrol bleeding in the wound or body cavity.